Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease

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Abstract

Background

Bilirubin has antioxidant properties against chronic respiratory diseases. However, previous studies are limited by acquisition of serum bilirubin level at one time point and its analysis with clinical parameters. We evaluated the association of serum bilirubin levels with various clinical outcomes of chronic obstructive pulmonary disease (COPD) in Korean Obstructive Lung Disease (KOLD) cohort.

Methods

We included 535 patients with COPD from the KOLD cohort. Serum bilirubin levels and various clinical parameters, such as lung function, 6-min walking (6 MW) distance, quality of life (QoL), and exacerbation, were evaluated annually; their association was analyzed using generalized estimating equations and the linear mixed model.

Results

Among 535 patients, 345 (64.5%) and 190 (35.5%) were categorized into Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II and GOLD III-IV groups, respectively. 6 MW distance was positively associated with serum bilirubin levels, especially in the GOLD I-II group (estimated mean = 41.5). Among QoL indexes, the COPD assessment test score was negatively associated with serum bilirubin levels only in the GOLD I-II group (estimated mean = − 2.8). Higher serum bilirubin levels were independently associated with a higher number of acute exacerbation in the GOLD III-IV group (estimated mean = 0.45, P = 0.001). Multivariate analysis revealed that lung function and mortality were not associated with serum bilirubin levels.

Conclusions

Higher serum bilirubin levels were associated with a longer 6 MW distance and better QoL, especially in the GOLD I-II group, whereas they were related to a higher risk of acute exacerbation, especially in the GOLD III-IV group. Bilirubin levels may represent various conditions in COPD.

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Most cited references 16

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Biliverdin reductase: a major physiologic cytoprotectant.

David Barañano, Mahil Rao, Christopher Ferris … (2002)

Bilirubin, an abundant pigment that causes jaundice, has long lacked any clear physiologic role. It arises from enzymatic reduction by biliverdin reductase of biliverdin, a product of heme oxygenase activity. Bilirubin is a potent antioxidant that we show can protect cells from a 10,000-fold excess of H2O2. We report that bilirubin is a major physiologic antioxidant cytoprotectant. Thus, cellular depletion of bilirubin by RNA interference markedly augments tissue levels of reactive oxygen species and causes apoptotic cell death. Depletion of glutathione, generally regarded as a physiologic antioxidant cytoprotectant, elicits lesser increases in reactive oxygen species and cell death. The potent physiologic antioxidant actions of bilirubin reflect an amplification cycle whereby bilirubin, acting as an antioxidant, is itself oxidized to biliverdin and then recycled by biliverdin reductase back to bilirubin. This redox cycle may constitute the principal physiologic function of bilirubin.

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Simvastatin for the prevention of exacerbations in moderate-to-severe COPD.

Paul Scanlon, Mark T Dransfield, Rachel Lazarus … (2014)

Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial. We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second [FEV1] of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers. A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (±SD) age of 62.2±8.4 years, an FEV1 that was 41.6±17.7% of the predicted value, and a smoking history of 50.6±27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36±1.61 exacerbations and 1.39±1.73 exacerbations, respectively (P=0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval [CI], 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P=0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P=0.89). Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.).

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The role of oxidative stress in skeletal muscle injury and regeneration: focus on antioxidant enzymes

Magdalena Kozakowska, Katarzyna Pietraszek-Gremplewicz, Alicja Jozkowicz … (2015)

Reactive oxygen species (ROS) are generated in skeletal muscle both during the rest and contractile activity. Myogenic cells are equipped with antioxidant enzymes, like superoxide dismutase, catalase, glutathione peroxidase, γ-glutamylcysteine synthetase and heme oxygenase-1. These enzymes not only neutralise excessive ROS, but also affect myogenic regeneration at several stages: influence post-injury inflammatory reaction, enhance viability and proliferation of muscle satellite cells and myoblasts and affect their differentiation. Finally, antioxidant enzymes regulate also processes accompanying muscle regeneration—induce angiogenesis and reduce fibrosis. Elevated ROS production was also observed in Duchenne muscular dystrophy (DMD), a disease characterised by degeneration of muscle tissue and therefore—increased rate of myogenic regeneration. Antioxidant enzymes are consequently considered as target for therapies counteracting dystrophic symptoms. In this review we present current knowledge regarding the role of oxidative stress and systems of enzymatic antioxidant defence in muscular regeneration after both acute injury and persistent muscular degeneration.

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Author and article information

Contributors

Ji Ye Jung:

ORCID: http://orcid.org/0000-0003-1589-4142

STOPYES@yuhs.ac

Journal

Journal ID (nlm-ta): Respir Res

Journal ID (iso-abbrev): Respir. Res

Title: Respiratory Research

Publisher: BioMed Central (London )

ISSN (Print): 1465-9921

ISSN (Electronic): 1465-993X

Publication date (Electronic): 9 December 2019

Publication date PMC-release: 9 December 2019

Publication date (Print): 2019

Volume: 20

Electronic Location Identifier: 279

Affiliations

[1 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Division of Pulmonology, Department of Internal Medicine, Institute of Chest Disease, , Yonsei University College of Medicine, ; 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea

[2 ]ISNI 0000 0004 0647 3511, GRID grid.410886.3, Department of Internal Medicine, CHA Bundang Medical Center, , CHA University, ; Seongnam, Republic of Korea

[3 ]ISNI 0000 0004 0647 3212, GRID grid.412145.7, Division of Pulmonary and Critical Care Medicine, , Hanyang University Guri Hospital, Hanyang University College of Medicine, ; Guri, Republic of Korea

[4 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Biostatistics Collaboration Unit, , Yonsei University College of Medicine, ; Seoul, Republic of Korea

[5 ]ISNI 0000 0004 0533 4667, GRID grid.267370.7, Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, , University of Ulsan College of Medicine, ; Seoul, Republic of Korea

Author information

Ji Ye Jung http://orcid.org/0000-0003-1589-4142

Article

Publisher ID: 1241

DOI: 10.1186/s12931-019-1241-5

PMC ID: 6902503

PubMed ID: 31818285

SO-VID: 1fa65d03-bd3c-4bf0-807f-4b7a110769c7

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 23 July 2019

Date accepted : 14 November 2019

Funding

Funded by: Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education

Award ID: 2016R1D1A1B03933125

Award Recipient : Ji Ye Jung

Custom metadata

ScienceOpen disciplines: Respiratory medicine

Keywords: chronic obstructive pulmonary disease,exercise,quality of life,bilirubin,exacerbation

Data availability:

ScienceOpen disciplines: Respiratory medicine

Keywords: chronic obstructive pulmonary disease, exercise, quality of life, bilirubin, exacerbation

Serum bilirubin level is associated with exercise capacity and quality of life in chronic obstructive pulmonary disease

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Abstract

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Biomarkers for Inflammatory Lung Disease

Most cited references 16

Biliverdin reductase: a major physiologic cytoprotectant.

Simvastatin for the prevention of exacerbations in moderate-to-severe COPD.

The role of oxidative stress in skeletal muscle injury and regeneration: focus on antioxidant enzymes

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